Inflammation is a critical protective biological process triggered by irritation, injury or infection, characterized by redness and heat (due to increased blood flow), swelling (due to increased vascular permeability), loss of function and pain (due to sensitization of pain receptors). In addition to the foregoing induced conditions, inflammation can also occur due to age related factors. The life expectancy of general population has increased dramatically during the past few decades due to the efficient control of the infectious diseases and better access to nutritious food. This positive enhancement in life span coupled with changing environmental conditions elevated the incidence of chronic age-related diseases such as arthritis, diabetes, cancer, cardiovascular diseases, etc. Chronic inflammatory conditions and cancer have become emerging health concerns in a number of countries across the globe and for people among all cultures. Arthritis is one of the most debilitating diseases of modern times. The quality of life for sufferers of these two diseases and their families is severely affected. Non-steroidal anti-inflammatory drugs are most commonly used remedies for rheumatic diseases. Presently, there has been a tremendous surge in demand for natural non-steroidal antiinflammatory drugs (NSAIDs) because of their established safety and efficacy, through decades of usage by various cultures.
The inflammatory and carcinogenesis processes are known to be triggered by increased metabolic activity of arachidonic acid. Arachidonic acid diverges down into two main pathways during this process, the cyclooxygenase (COX) and lipooxygenase (LOX) pathways. The COX pathways lead to prostaglandin and thromboxane production and the LOX pathways leads to leukotrienes (LTS) and 5(S)-hydroxy-6,8,11,14-E,Z,Z,Z-eicosatetraenoic acid [5(S)-HETEs]. These classes of inflammatory molecules exert profound biological effects, which enhance the development and progession of human cancers (Ding, X. Z., et. al., Pancreatology. 2001; 1(4):291-9).
Leukotrienes and 5(S)-HETE are important mediators for inflammatory, allergic and obstructive process. Leukotrienes increase microvascular permeability and are potent chemotactic agents. Inhibition of 5-lipooxygenase indirectly reduces the expression of TNF-α (a cytokine that plays a key role in inflammation). 5-Lipoxygenase is therefore the target enzyme for identifying inhibitors, which have potential to cope with a variety of inflammations and hypersensitivity-based human diseases including asthma, arthritis, bowel diseases such as ulcerative colitis and circulatory disorders such as shock and ischaemia.
Similarly prostaglandins are intercellular messengers that are produced in high concentration at the sites of chronic inflammation and are capable of causing vasodilation, increased vascular permeability and sensitizing pain receptors. The pro-inflammatory prostaglandins (PGE2) are produced by inducible isoform cyclooxygenase-2 (COX-2). The prostaglandins that are important in gastrointestinal and renal function are produced by the constitutively expressed isoform, cyclooxygenase-1 (COX-1). COX-1 is the protective housekeeper isoform and it regulates mucosal cell production of mucous that provides a barrier between the acid and pepsin present in gastric secretions. Non-selective COX inhibitors thus produce serious side effects. Scientists around the world are thus investing a major effort in identifying non-steroidal anti-inflammatory drugs that inhibit 5-lipoxygenase and cyclooxygenase-2 enzymes. As both COX-2 and 5-LOX are commonly expressed in any kind of inflammatory condition, efforts are currently being focused to obtain the so called dual acting anti-inflammatory drugs that are able to inhibit both COX-2 and 5-LOX enzymes. Unfortunately, the odds of finding a new dual acting natural NSAID that can truly alleviate the symptoms of inflammatory diseases are very thin. Hence, the researchers conceived the idea that using a combination of drugs, one having the COX-2 inhibitory activity and the other having 5-LOX inhibitory activity, as the next best option.
Rheumatoid arthritis is a chronic inflammatory condition that affects the lubricating mechanism and cushioning of joints. As a result of this autoimmune disease the bone surfaces are destroyed, which leads to stiffness, swelling, fatigue and crippling pain. Osteoarthritis is the common form of arthritis and results primarily from progressive degeneration of cartilage glycoaminoglycons. The damage is often compounded by a diminished ability to restore and repair joint structures including cartilage. The smooth surface of the cartilage becomes hard and rough, creating friction. As a result of this, the joint gets deformed, painful and stiff. Studies have indicated that over 40 million Americans have osteoarthritis, including 80% of persons over the age of 50. The major focus for osteoarthritis treatment, should therefore involve agents that not only stimulate the production of biological substances necessary for regeneration of cartilage cells and proper joint function but also diminish pain inflammation.
It is therefore an object of the present invention to provide a non-toxic supplement, which exhibits anti-arthritic and anti-inflammatory properties without deleterious side effects.
It is also an object of the present invention to provide a composition, which is useful both as an anti-cancer agent and anti-oxidant.